Parkinson's Disease
Conditions
Brief summary
This is a multi-center, international, open-label, safety study of ND0612, a solution of levodopa/carbidopa (LD/CD) delivered via a pump system as a continuous SC infusion in subjects with advanced Parkinson's Disease (PD).
Detailed description
This is a multi-center, international, open-label, safety study of ND0612, a solution of LD/CD delivered via a pump system as a continuous SC infusion in subjects with advanced PD. Two cohorts of subjects are candidates for this study: subjects who completed treatment in study ND0612H-006 within one month prior to enrollment (Cohort 1) and ND0612 naïve subjects or subjects who completed treatment in a ND0612 clinical study more than one month before screening (Cohort 2). After screening procedures and confirmation of the inclusion/exclusion criteria, subjects and their study partners will be trained and assisted at their homes during the first week of treatment on the proper operation of the pump system. One mandatory home visit will be performed during the first week and then on a monthly basis during 12-months of treatment. Subjects will return for in-clinic visits at Week 1 and at Months 1, 2, 3, 4, 6, 9, and 12 for assessment of safety and efficacy variables. Subjects will be allowed to continue with study treatment for an optional treatment extension period of up to Month 102 and the clinic visits will be performed every 3 months to assess subject long-term safety. Safety follow-up visits will occur 1, 2, and 3 months after the last SC infusion of ND0612 or after early termination.
Interventions
DRUGND0612
ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system
Sponsors
NeuroDerm Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Cohort 1. 1. Subject is able to, and has signed an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF). 2. Subject has completed the treatment period of study ND0612H-006 not more than one month prior to enrolling in ND0612H-012. 3. Willing and able to administer the SC infusion alone or with the assistance of a study partner and able to comply with the study specific procedures. Cohort 2. 1. Male and female PD subjects of any race aged at least 30 years who sign an IRB/EC-approved ICF. 2. PD diagnosis consistent with the UK Brain Bank Criteria. 3. Modified Hoehn & Yahr scale in ON state of stage ≤3. 4. Taking at least 4 doses/day of LD/DDI (or at least 3 doses/day of Rytary) and taking, or have attempted to take, at least one other PD treatment for at least 30 days. 5. Subjects must be stable on their anti-PD medications for at least 30 days before Day 1. 6. Subjects may have had prior exposure to SC apomorphine injections/infusion but must have stopped continuous apomorphine administration at least 4 weeks before the screening visit. Treatment with apomorphine is prohibited during the entire ND0612 treatment period. 7. Must have a minimum of 2 hrs of OFF time per day with predictable early morning OFF periods as estimated by the subject. 8. Must have predictable and well defined early morning OFF periods with a good response to LD for treatment of the early morning OFF in the judgement of the investigator. 9. Mini Mental State Examination (MMSE) score ≥26. 10. No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or non-compliant in the study. 11. Female subjects must be surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation), postmenopausal (defined as cessation of menses for at least 1 year), or willing to practice a highly effective method of contraception. All female participants must be non-lactating and non-pregnant and have a negative urine pregnancy test at Screening and at Baseline. Female subjects of childbearing potential must practice a highly effective method of contraception (e.g., oral contraceptives, intrauterine devices, partner with vasectomy), 1 month before enrollment, for the duration of the study, and 3 months after the last dose of study drug. Alternatively, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active, the subject and sexual partner must comply with the contraceptive requirements detailed above. 12. Willing and able to administer the SC infusion alone or with the assistance of a study partner after a screening period of up to 40 days and willing and able to comply with study requirements. 13. Subjects should have a named study partner.
Exclusion criteria
Cohort 1 and 2. Previously unable to tolerate ND0612 and/or have experienced intolerable adverse drug reactions associated with its use, regardless of the dosing regimen administered. Cohort 2. 1. Atypical or secondary parkinsonism. 2. Acute psychosis or hallucinations in past 6 months. 3. Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study. 4. Any malignancy in the 5 years prior to randomization (excluding basal cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated). 5. Positive serum serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) at the Screening visit. 6. Prior neurosurgical procedure for PD, or Duodopa treatment 7. Subjects with a history of drug abuse or alcoholism within the past 12 months. 8. Clinically significant ECG rhythm abnormalities. 9. Renal or liver dysfunction that may alter drug metabolism including: serum creatinine \>1.3 mg/dL, serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2 x upper limit of normal (ULN), total serum bilirubin \>2.5 mg/dL. 10. Current participation in a clinical trial with an investigational product or past participation within the last 30 days before Day 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (Long-term Safety) | Baseline to Month 12 | Long-term safety (systemic and local) assessment will be based on adverse events (AEs), with a focus on adverse events of special interest (AESI), i.e., infusion site reactions, cases of hypersensitivity, polyneuropathy. |
| Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability) | Baseline to Month 12 | Tolerability will be assessed based on the percentage of subjects that complete the 12-month treatment period of the study and the percentage of subjects who discontinue from the 12-month treatment period due to an AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (Long-term Safety) | Month 12 to Month 102 | Long-term safety (systemic and local) and tolerability will be based on AEs, with a focus on AESI, i.e., infusion site reactions, cases of hypersensitivity, polyneuropathy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Responders | Baseline to Month 12 | Exploratory endpoint. A responder is defined as a subject that experiences ≥50% reduction in OFF time from Baseline. Improvement of ≥50% in OFF time will be assessed based on home ON/OFF diaries and normalized to 16 hours of awake time. |
| Change of Daily ON Time With Troublesome Dyskinesia | Baseline to Month 12 | Exploratory endpoint. Daily ON time with troublesome dyskinesia will be assessed based on home ON/OFF diaries in a subset of subjects who had more than 1 hour of troublesome dyskinesia at baseline. It will be normalized to 16 hours of awake time. |
| Change of PDQ-39 Scores | Baseline to Month 12 | Exploratory endpoint. Quality of Life in Parkinson's Disease (PDQ)-39 is a 39-item, self-administered questionnaire with 8 discrete dimensions (mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort.). The PDQ-39 Summary Index is the sum of the dimension scores divided by the number of dimensions. Higher scores indicate a worse quality of life. |
| Change of EQ-5D-5L Scores | Baseline to Month 12 | Exploratory endpoint. The perception of general quality of life (QoL) will be rated by the subjects using the EuroQoL 5-dimensions 5-severity levels (EQ-5D-5L) questionnaire. The EQ-5D-5L consists of 2 pages, the EQ-5D-5L descriptive system and the EQ Visual Analogue Scale (VAS). The descriptive system comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20 cm vertical VAS with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. Decrease in the 5-dimensions scores and increase in EQ VAS score will indicate improvement. |
| Change of UPDRS Part II (ADL) | Baseline to Month 12 | Exploratory endpoint. The Unified Parkinson's disease rating scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS Part II (activity of daily living) score was calculated as the sum of the individual UPDRS items 5-17. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). Higher scores correlate with greater impairments for daily activities. |
| Change in CGI-Severity and CGI-Improvement | Baseline to Month 12 | Exploratory endpoint. Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) are rated by the investigator or designee. CGI-S employs a 7-point scale with 1 being not at all ill and 7 being among the most severely ill subjects for severity rating. The CGI-I employs a 7-point scale with 1 being very much improved and 7 being very much worse for improvement rating. |
| Change of Daily ON Time Without Troublesome Dyskinesia | Baseline to Month 12 | Exploratory endpoint. ON time without troublesome dyskinesia is defined as the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia. Daily ON time without troublesome dyskinesia will be assessed based on home ON/OFF diaries and normalized to 16 hours of awake time. |
| Change in PDSS-2 Total Score | Baseline to Month 12 | Exploratory endpoint. The quality of night sleep is rated by the subjects using the Parkinson's Disease Sleep Scale (PDSS)-2, which includes questions addressing 15 commonly reported symptoms associated with sleep disturbance in PD. Higher scores indicate a lower quality of sleep, i.e., a reduction in the score indicates an improvement in sleep quality. |
| Change in UPDRS Part III (Motor Score) | Baseline to Month 12 | Exploratory endpoint. The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. UPDRS part III (motor) score is calculated as the sum of the individual UPDRS items 18-31, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). Higher scores correlate with greater motor impairment. |
| Change in Percentage of OFF Time and Percentage of Good ON During the First 3 Hours Since the Subject is Awake After 06:00 (6 am) | Baseline to Month 12 | Exploratory endpoint. Good ON time (or ON time without troublesome dyskinesia) is defined as the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia. For this endpoint, Good ON time and OFF time will be assessed based on home ON/OFF diaries during the first 3 hours since the subject is awake after 06:00 (6 am). |
| Change in ND0612 Total Dose | Baseline to Month 12 | Exploratory endpoint. Change in ND0612 total daily dose. |
| Proportion of Patients Who Reduced ND0612 Total Dose | Baseline to Month 102 | Exploratory endpoint. Proportion of patients who reduced ND0612 total dose at any time during the study. |
| Change in SGI-Improvement | Baseline to Month 12 | Exploratory endpoint. Subjects Global Impression of Improvement (SGI-I) is rated by the subject. The SGI-I employs a 7-point scale with 1 being very much improved and 7 being very much worse for improvement rating. |
| Change of Daily OFF Time | Baseline to Month 12 | Exploratory endpoint. Daily OFF time will be assessed based on home ON/OFF diaries and normalized to 16 hours of awake time. |
| Change of Total Daily Dose of Oral LD/DDI | Baseline to Month 12 | Exploratory endpoint. Total daily dose of oral Levodopa (LD)/Dopa-Decarboxylase Inhibitor (DDI). |
Countries
Austria, Czechia, France, Germany, Israel, Italy, Poland, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 24-hour Dosing Regimen Continuous SC infusion over 24 hours: fixed day rate of up to 0.64 mL/h for 18 hours, followed by a night rate of 0.08 mL/h for 6 hours to deliver a total daily dose of up to 720/90 mg of levodopa/carbidopa.
All patients who had been previously assigned to the 24-hour group in the prior study continued on this dosing regimen; patients who had previously been assigned to the 14-hour daytime regimen were switched to the 24-hour regimen.
ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system | 90 |
| 16-hour Dosing Regimen Continuous SC infusion for over 16 hours: fixed rate of 0.75 mL/h to deliver a total infusion dose of 720/90 mg of levodopa/carbidopa over 16 hours.
The device is removed at night and patients in this group also receive a morning oral dose of levodopa/carbidopa upon awakening.
ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system | 124 |
| Total | 214 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 20 |
| Overall Study | Other reasons | 7 | 8 |
| Overall Study | Withdrawal by Subject | 14 | 28 |
Baseline characteristics
| Characteristic | 24-hour Dosing Regimen | 16-hour Dosing Regimen | Total |
|---|---|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 8.9 | 63.9 years STANDARD_DEVIATION 8.9 | 64.0 years STANDARD_DEVIATION 8.9 |
| Age, Customized Age (years) <65 years | 43 Participants | 63 Participants | 106 Participants |
| Age, Customized Age (years) ≥65 years | 47 Participants | 61 Participants | 108 Participants |
| BMI <20 kg/m2 | 11 Participants | 11 Participants | 22 Participants |
| BMI ≥20 kg/m2 | 79 Participants | 113 Participants | 192 Participants |
| BMI | 27.0 kg/m^2 STANDARD_DEVIATION 5.5 | 27.2 kg/m^2 STANDARD_DEVIATION 5.9 | 27.1 kg/m^2 STANDARD_DEVIATION 5.7 |
| Concomitant medications Amantadine | 25 Participants | 30 Participants | 55 Participants |
| Concomitant medications COMT inhibitors | 28 Participants | 24 Participants | 52 Participants |
| Concomitant medications Dopamine agonists | 52 Participants | 58 Participants | 110 Participants |
| Concomitant medications MAO-B inhibitors | 37 Participants | 44 Participants | 81 Participants |
| MMSE total score | 28.8 Points STANDARD_DEVIATION 1.2 | 28.8 Points STANDARD_DEVIATION 1.2 | 28.8 Points STANDARD_DEVIATION 1.2 |
| Modified Hoehn & Yahr 2 | 37 Participants | 52 Participants | 89 Participants |
| Modified Hoehn & Yahr <2 | 4 Participants | 5 Participants | 9 Participants |
| Modified Hoehn & Yahr 2.5 | 17 Participants | 32 Participants | 49 Participants |
| Modified Hoehn & Yahr 3 | 32 Participants | 35 Participants | 67 Participants |
| Race/Ethnicity, Customized Ethnicity Caucasian | 86 Participants | 116 Participants | 202 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 4 Participants | 8 Participants | 12 Participants |
| Sex: Female, Male Female | 32 Participants | 40 Participants | 72 Participants |
| Sex: Female, Male Male | 58 Participants | 84 Participants | 142 Participants |
| Time since onset of fluctuations | 5.3 years STANDARD_DEVIATION 4.3 | 5.2 years STANDARD_DEVIATION 4.2 | 5.3 years STANDARD_DEVIATION 4.2 |
| Time since PD diagnosis | 10.6 years STANDARD_DEVIATION 5.3 | 7.9 years STANDARD_DEVIATION 3.8 | 9.0 years STANDARD_DEVIATION 4.7 |
| Total daily levodopa dose | 1090 mg STANDARD_DEVIATION 623 | 1004 mg STANDARD_DEVIATION 540 | 1040 mg STANDARD_DEVIATION 577 |
| Total daily levodopa frequency | 5.9 Times per day STANDARD_DEVIATION 2.2 | 5.1 Times per day STANDARD_DEVIATION 1.7 | 5.5 Times per day STANDARD_DEVIATION 2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 90 | 1 / 124 |
| other Total, other adverse events | 69 / 90 | 82 / 124 |
| serious Total, serious adverse events | 17 / 90 | 14 / 124 |
Outcome results
Primary
Adverse Events (Long-term Safety)
Long-term safety (systemic and local) assessment will be based on adverse events (AEs), with a focus on adverse events of special interest (AESI), i.e., infusion site reactions, cases of hypersensitivity, polyneuropathy.
Time frame: Baseline to Month 12
Population: Safety set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 24-hour Dosing Regimen | Adverse Events (Long-term Safety) | Drug-related TEAEs | 65 Participants |
| 24-hour Dosing Regimen | Adverse Events (Long-term Safety) | Serious TEAEs | 17 Participants |
| 24-hour Dosing Regimen | Adverse Events (Long-term Safety) | Infusion site TEAEs | 55 Participants |
| 24-hour Dosing Regimen | Adverse Events (Long-term Safety) | Death | 0 Participants |
| 24-hour Dosing Regimen | Adverse Events (Long-term Safety) | Any TEAE | 78 Participants |
| 16-hour Dosing Regimen | Adverse Events (Long-term Safety) | Death | 1 Participants |
| 16-hour Dosing Regimen | Adverse Events (Long-term Safety) | Any TEAE | 105 Participants |
| 16-hour Dosing Regimen | Adverse Events (Long-term Safety) | Drug-related TEAEs | 78 Participants |
| 16-hour Dosing Regimen | Adverse Events (Long-term Safety) | Infusion site TEAEs | 66 Participants |
| 16-hour Dosing Regimen | Adverse Events (Long-term Safety) | Serious TEAEs | 14 Participants |
Primary
Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability)
Tolerability will be assessed based on the percentage of subjects that complete the 12-month treatment period of the study and the percentage of subjects who discontinue from the 12-month treatment period due to an AE.
Time frame: Baseline to Month 12
Population: Intention-to-Treat (ITT) set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 24-hour Dosing Regimen | Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability) | Completed the 12-month treatment period | 52 Participants |
| 24-hour Dosing Regimen | Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability) | Discontinued due to AE | 17 Participants |
| 16-hour Dosing Regimen | Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability) | Completed the 12-month treatment period | 68 Participants |
| 16-hour Dosing Regimen | Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability) | Discontinued due to AE | 20 Participants |
Secondary
Adverse Events (Long-term Safety)
Long-term safety (systemic and local) and tolerability will be based on AEs, with a focus on AESI, i.e., infusion site reactions, cases of hypersensitivity, polyneuropathy.
Time frame: Month 12 to Month 102
Other Pre-specified
Change in CGI-Severity and CGI-Improvement
Exploratory endpoint. Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) are rated by the investigator or designee. CGI-S employs a 7-point scale with 1 being not at all ill and 7 being among the most severely ill subjects for severity rating. The CGI-I employs a 7-point scale with 1 being very much improved and 7 being very much worse for improvement rating.
Time frame: Baseline to Month 12
Other Pre-specified
Change in ND0612 Total Dose
Exploratory endpoint. Change in ND0612 total daily dose.
Time frame: Baseline to Month 12
Other Pre-specified
Change in PDSS-2 Total Score
Exploratory endpoint. The quality of night sleep is rated by the subjects using the Parkinson's Disease Sleep Scale (PDSS)-2, which includes questions addressing 15 commonly reported symptoms associated with sleep disturbance in PD. Higher scores indicate a lower quality of sleep, i.e., a reduction in the score indicates an improvement in sleep quality.
Time frame: Baseline to Month 12
Other Pre-specified
Change in Percentage of OFF Time and Percentage of Good ON During the First 3 Hours Since the Subject is Awake After 06:00 (6 am)
Exploratory endpoint. Good ON time (or ON time without troublesome dyskinesia) is defined as the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia. For this endpoint, Good ON time and OFF time will be assessed based on home ON/OFF diaries during the first 3 hours since the subject is awake after 06:00 (6 am).
Time frame: Baseline to Month 12
Other Pre-specified
Change in SGI-Improvement
Exploratory endpoint. Subjects Global Impression of Improvement (SGI-I) is rated by the subject. The SGI-I employs a 7-point scale with 1 being very much improved and 7 being very much worse for improvement rating.
Time frame: Baseline to Month 12
Other Pre-specified
Change in UPDRS Part III (Motor Score)
Exploratory endpoint. The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. UPDRS part III (motor) score is calculated as the sum of the individual UPDRS items 18-31, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). Higher scores correlate with greater motor impairment.
Time frame: Baseline to Month 12
Other Pre-specified
Change of Daily OFF Time
Exploratory endpoint. Daily OFF time will be assessed based on home ON/OFF diaries and normalized to 16 hours of awake time.
Time frame: Baseline to Month 12
Other Pre-specified
Change of Daily ON Time Without Troublesome Dyskinesia
Exploratory endpoint. ON time without troublesome dyskinesia is defined as the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia. Daily ON time without troublesome dyskinesia will be assessed based on home ON/OFF diaries and normalized to 16 hours of awake time.
Time frame: Baseline to Month 12
Other Pre-specified
Change of Daily ON Time With Troublesome Dyskinesia
Exploratory endpoint. Daily ON time with troublesome dyskinesia will be assessed based on home ON/OFF diaries in a subset of subjects who had more than 1 hour of troublesome dyskinesia at baseline. It will be normalized to 16 hours of awake time.
Time frame: Baseline to Month 12
Other Pre-specified
Change of EQ-5D-5L Scores
Exploratory endpoint. The perception of general quality of life (QoL) will be rated by the subjects using the EuroQoL 5-dimensions 5-severity levels (EQ-5D-5L) questionnaire. The EQ-5D-5L consists of 2 pages, the EQ-5D-5L descriptive system and the EQ Visual Analogue Scale (VAS). The descriptive system comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20 cm vertical VAS with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. Decrease in the 5-dimensions scores and increase in EQ VAS score will indicate improvement.
Time frame: Baseline to Month 12
Other Pre-specified
Change of PDQ-39 Scores
Exploratory endpoint. Quality of Life in Parkinson's Disease (PDQ)-39 is a 39-item, self-administered questionnaire with 8 discrete dimensions (mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort.). The PDQ-39 Summary Index is the sum of the dimension scores divided by the number of dimensions. Higher scores indicate a worse quality of life.
Time frame: Baseline to Month 12
Other Pre-specified
Change of Total Daily Dose of Oral LD/DDI
Exploratory endpoint. Total daily dose of oral Levodopa (LD)/Dopa-Decarboxylase Inhibitor (DDI).
Time frame: Baseline to Month 12
Other Pre-specified
Change of UPDRS Part II (ADL)
Exploratory endpoint. The Unified Parkinson's disease rating scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS Part II (activity of daily living) score was calculated as the sum of the individual UPDRS items 5-17. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). Higher scores correlate with greater impairments for daily activities.
Time frame: Baseline to Month 12
Other Pre-specified
Proportion of Patients Who Reduced ND0612 Total Dose
Exploratory endpoint. Proportion of patients who reduced ND0612 total dose at any time during the study.
Time frame: Baseline to Month 102
Other Pre-specified
Proportion of Responders
Exploratory endpoint. A responder is defined as a subject that experiences ≥50% reduction in OFF time from Baseline. Improvement of ≥50% in OFF time will be assessed based on home ON/OFF diaries and normalized to 16 hours of awake time.
Time frame: Baseline to Month 12